The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
The cdr1B efflux transporter is associated with non-cyp51a-mediated itraconazole resistance in Aspergillus fumigatus
Open accessAbstract
OBJECTIVES: Recent increases in triazole resistance in Aspergillus fumigatus have been attributed primarily to target site (cyp51A) mutations. A recent survey of resistant isolates in Manchester showed that >50% of resistant isolates had no mutation in cyp51A or its promoter. We investigated the mechanisms of resistance in clinical azole-resistant isolates without cyp51A mutations. METHODS: Twelve azole-resistant isolates, 10 of which were itraconazole resistant, were studied. Bioinformatic comparisons between Candida albicans efflux genes and A. fumigatus genome data identified 20 putative azole transporter genes. Basal and azole-induced expression of these genes and cyp51A was quantified using RT-PCR with comparison with clinical azole-susceptible isolates. Function of high basal or itraconazole-induced expression transporters was tested by gene knockout in azole-susceptible and azole-resistant isolates. RESULTS: All susceptible strains showed minimal basal expression of cdr1B compared with 8 of 10 azole-resistant strains with high basal expression of this gene (>5-fold), 3 of which showed >30-fold increased expression. Knockout of this gene resulted in a 4-fold reduction in itraconazole, posaconazole and voriconazole MICs for a susceptible clinical isolate and a 4-fold reduction in itraconazole susceptibility in a clinical resistant isolate. One strain showed a >500-fold induction of cyp51A. No increase in basal expression or expression after induction was seen for the 18 remaining putative transporters. CONCLUSIONS: The reasons behind the shift away from target site mutation in azole-resistant isolates from Manchester are unknown. The modest change in expression of cdr1B in azole-susceptible strains implies that only study of resistant isolates will lead to further understanding of resistance mechanisms in A. fumigatus.
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Cites
Resistance Mechanisms in Clinical Isolates of Candida albicans
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An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1
Selmecki, A., Gerami‐Nejad, M., Paulson, C., Forche, A., & Berman, J. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06176.x · Cited by 325
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Self-citationMechanism of Increased Fluconazole Resistance in Candida glabrata during Prophylaxis
Bennett, J. E., Izumikawa, K., & Marr, K. A. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.5.1773-1777.2004 · Cited by 217
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Cited by
Ullmann, A. J., Aguado, J. M., Arikan-Akdagli, S., Denning, D. W., Groll, A. H., Lagrou, K., Lass-Flörl, C., Lewis, R. E., Munoz, P., Verweij, P. E., et al. (2018) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2018.01.002 · Cited by 1,556
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Mechanisms of Antifungal Drug Resistance
Cowen, L. E., Sanglard, D., Howard, S. J., Rogers, P. D., & Perlin, D. S. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019752 · Cited by 647
Clinical implications of globally emerging azole resistance in Aspergillus fumigatus
Meis, J. F., Chowdhary, A., Rhodes, J. L., Fisher, M. C., & Verweij, P. E. (2016) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2015.0460 · Cited by 308
Scedosporium and Lomentospora: an updated overview of underrated opportunists
Ramirez-Garcia, A., Pellon, A., Rementeria, A., Buldain, I., Barreto-Bergter, E., Rollin-Pinheiro, R., de Meirelles, J. V., Xisto, M. I. D. S., Ranque, S., Havlicek, V., et al. (2018) · Medical Mycology · doi:10.1093/mmy/myx113 · Cited by 264
Metadata
- Authors
- Fraczek, M. G., Bromley, M., Buied, A., Moore, C. B., Rajendran, R., Rautemaa, R., Ramage, G., Denning, D. W., & Bowyer, P.
- Venue
- Journal of Antimicrobial Chemotherapy
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-04-10
- Volume
- 68
- Issue
- 7
- Pages
- 1486-1496
- ISSN
- 0305-7453 (ISSN-L)
- 1460-2091
- OpenAlex
- W2118505677
- Cited by
- 315
- References
- 10
- FWCI
- 9.87
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Fraczek, M. G., Bromley, M., Buied, A., Moore, C. B., Rajendran, R., Rautemaa, R., Ramage, G., Denning, D. W., & Bowyer, P. (2013). The cdr1B efflux transporter is associated with non-cyp51a-mediated itraconazole resistance in Aspergillus fumigatus. Journal of Antimicrobial Chemotherapy. https://doi.org/10.1093/jac/dkt075
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